1. Field of the Invention
The present invention relates to new derivatives of benzopyrene glycosides, their method of production as well as their use in human therapy.
2. Description of the Prior Art
The benzopyran glycosides form a class of compounds containing derivatives such as rutin, hesperidin, esculin, and naringin, and which exhibit multiple pharmacological and biological properties, among which is a reduction of capillary fragility, which is often related to their inhibitory activity with respect to catechol O-methyl transferase, and which is generally associated with an anti-edemic activity. Certain of these derivatives are also inhibitors of aldose reductase, an enzyme which has been implicated in particular in the development of cataracts and neuropathies among diabetics. Certain of these compounds are employed in therapy, most often in the treatment of capillary fragility.
Several partial synthetic procedures have been developed by various laboratories for the purpose of preparing derivatives which are more active or which present improved physicochemical properties, such as greater solubility in water. Examples of procedures for etherification of one or more phenolic functions of the quercetin nucleus of rutin include etherification by hydroxyethyl groups (hydroxyethyl rutoside), methyl groups (methyl rutin), and morpholinoethyl groups (ethoxazorutin).
These methods have the disadvantage of leading to more or less well defined mixtures and of blocking one or more phenolic OH functions. Thus, the hydroxyethylation of rutin leads to a mixture containing as major constituents the 5, 7, 4'-tri-O-hydroxyethyl, 7, 3', 4'-tri-O-hydroxyethyl, 5, 7, 3',4'-tetra-O-hydroxyethyl, 7, 4'-di-O-hydroxyethyl and 4'-mono-O-hydroxyethyl derivatives. Furthermore, since rutin inhibits aldose reductase in vitro, the derivatives in which one or more phenolic OH groups are blocked, such as 7-O-hydroxyethyl rutin, 7, 3', 4'-tri-O-hydroxyethyl rutin and 5, 7, 3', 4'-tetra-O-hydroxyethyl rutin are practically inactive.
A need therefore continues to exist for derivatives of benzopyran glycosides having improved pharmacological and biological activity and improved properties such as greater solubility in water, without diminishing aldose reductase inhibitory activity. A need also exists for a method for preparing specific derivatives of benzopyran glycosides as pure compounds.